Funds are requested to purchase an Ivis Spectrum CT optical and computed tomography (CT) imaging system (Caliper Life Sciences, Hopkinton, MA) for quantitative in vivo bio photonic (i.e. bioluminescent and fluorescent) imaging for non-invasively and longitudinally monitoring (a) cancer and other disease processes, (b) trafficking of cancer, immune, and stem cells, (c) cellular responses to therapy and other interventions, and (d) genetic pathway expression in small-animal (i.e. mouse and rat) tumor models. Like our two existing Ivis systems, the Ivis 100 and 200, this state-of-the-art instrument, to be installed n our Small-Animal Imaging Core Facility, will be a critical, broadly used component of the pre-clinical and translational oncology research program at Memorial Sloan-Kettering Cancer Center (MSKCC). In vivo bioluminescent and fluorescent imaging has rapidly become a staple of pre-clinical biomedical research world-wide. However, both our Ivis 100 and 200 systems are used very heavily (and, now beyond capacity) and their use continues to increase - they are by far the most heavily used of our small-animal imaging instruments, supporting up to three dozen laboratories throughout MSKCC. Thus, there is no back-up/redundancy. When one of these systems requires service, therefore, experimental work is delayed and potentially compromised and even lost. Further, the Ivis 100 and 200 are now 9- and 6-years-old, respectively, and approaching or already beyond their useful lifespan and thus subject to irreparable failure at any moment. Besides providing urgently needed additional imaging capacity and back-up, the Ivis Spectrum CT would provide critical new functionality, including (1) trans-illumination fluorescence imaging in both the optical and near-infrared (NIR) range, providing far better spectral resolution and fluorescence-imaging contrast; (2) three-dimensional (3D)/ tomographic imaging capability to provide critical depth information; and (3) integrated CT-based 3D imaging to allow seamless near-perfect registration of optical and anatomic images and thereby unambiguous localization in vivo of optical signal foci. Our Facility and Center have well-established technical and scientific expertise to fully and immediately utilize this instrument upo its installation and an efficient administrative and financial infrastructure to support and maintan this instrument and its effective use long-term.